P1337: SURVIVAL EFFICACY OF MDS/AML PATIENTS WITH TP53 GENE ALTERATION RECEIVED ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: D. Feng, E. Jiang
Journal: HemaSphere (2022)

Background: Although not yet included in guidelines, TP53 mutations are undoubtedly one of the undesirable factors in the risk prognosis of medullary tumors in the hematologic system. Different TP53 gene states have different prognostic effects on MDS and AML, and whether allogeneic hematopoietic stem cell transplantation can overcome this undesirable factor needs to be further explored. Aims: To investigate the survival efficacy of allo-geneic hematopoietic stem cells in patients with MDS/AML with TP53 state changes (deletion, monoallelic mutation, multi-hit). Analyzing the clinical characteristics in patients with different TP53 gene alterations, and further exploring the influencing factors of clinical prognosis of TP53-change MDS/AML after allo-HSCT. Methods: A retrospective analysis was conducted on 42 patients with TP53-MDS/AML who underwent allo-HSCT from 2006.1 to 2021.7.These patients may have deletion of the TP53 gene and/or mutations in the TP53 gene.The 42 patients were divided into 3 groups,TP53 deletion MDS/AML group (group A), TP53 mono-mutation MDS/AML group (group B), and TP53 multiple-hits group (group C), and the differences in clinical features and the effect on the prognosis of inhibition were analyzed.The changes in the characteristics of second-generation sequencing of 137 genes in bone marrow specimens of 29 patients with mutations were also discussed. Results: There were 42 MDS/AML patients, 30 males (71.4%), 12 females (28.6%), 21 MDS patients, 1 MDS-AML patient, and 20 AML patients. The average age of patients at the time of transplantation was 42 years, of which 11 patients with only TP53 deficiency (26.1%), 25 patients with TP53 single mutation (59.5%), and 6 patients with TP53 multiple hits (14.2%). Among the 42 patients, 14 (33.3%) died, 10 cases relapsed (23.8%), and the overall patients who received hematopoietic stem cell transplantation had 3 years OS＞40%,and there was no statistical difference in 3 years OS in group A, B and C. Univariate analysis shows,hemoglobin、age of HSCT、complex karyotype、pre-HSCT MRD were risk factors for survival (p=0.003,p=0.042,p=0.009,p=0.004), and TP53 stage、co-mutation、treatment before HSCT、type of Diseases not. Complex karyotype、hemoglobin、pre-HSCT MRD were also risk factors for relapse (p=0.038,p=0.02,p=0.023),besides,pre-HSCT BM blast% also have an impact on relapse,p=0.027.Among the 42 patients, 12 patients (28.5%) with complex karyotype, including 2 patients with TP53 deletion alone (16.6%), 5 patients with TP53 single mutation (41.6%), and 5 patients with TP53 multiple hit (41.6%).Of the 12 patients with complex karyotypes, 7 died, 5 relapsed, and 4 of the 7 deaths were patients with TP53 multi-hits. Survival and relapse of TP53 mutations may be associated with complex karyotype (p=0.009,p=0.038). Summary/Conclusion: Allo-hematopoietic stem cell transplantation can overcome the poor changes of MDS/AML patients with TP53 mutation/deletion, but complex karyotype is still a poor prognostic factor for TP53-MDS/AML patients receiving allo-HSCT.